Virology Dr. Belal Azab

د. بالل العزب

Email: azab.belalm@gmail.com

Office location: SOM 140 Cell Therapy Center

First Semester 2018-2019

We live and prosper in a cloud of viruses● Viruses are everywhere!! Inside our bodies or around us and even in the air

we breathe in.

● We regularly eat and breath billions of virus particles.

● Viruses infect every living thing in the planet.

● We carry genomes as part of our own genetic material

The number of viruses on earth staggering ● The whole game with viruses is numbers, they make huge numbers of

progeny and maybe a few of them end up infecting a cell and moving on; because life is hard out there for a virus.

● The number of viruses on earth is amazing, just in the oceans alone there are 1030 bacteriophages (the virus that infect bacteria).

● In the oceans of the world about a million virus per teaspoon.

How infected we are?● We are all infected.● We all are infected with some kind of herpes virus

for sure.● You probably got at least 2 of them up to now, as

there is:- Herpes-simplex I (HSV-1)-Herpes-simplex II (HSV-2)-Varicella zoster virus (VZV)-Epstein-barr virus (EBV)-Cytomegalovirus (HCMV)-Human herpesvirus 6 (HHV-6)-Human herpesvirus 7 (HHV-7)-Human herpesvirus 8 (HHV-8)

EBV causes mononucleosis aka "mono." aka "kissing disease" because of one way you can spread it to someone else

How infected we are?

● You get Herpes virus quite young in age, most of them from your parents.● Through their saliva, and they already have HV.● Once infected it is for life.● We have no way to cure anyone from herpes.

Microbiome● Microbiome: bacteria that colonize every

organ system of the body.● The figure shows some of the bacteria

that inhibits some parts of the body, we have for example skin microbiome that differ greatly from one person to another, and even from the right to left hand.

● Now like we have microbiome we have virome

Virome● Even though it is as important as microbiome it doesn't get the same

attention. Maybe because it is harder to enumerate the virome.

● To study microbiome all you need to do is to extract some nucleic acid from the sample (for example from skin swap or stool sample) after extracting the nucleic acid, you sequence the rRNA, then you will have an idea about what bacteria inhabit the sample.

● The case with the virome is different, because viruses don't have a common sequence (like the bacteria have rRNA) to identify the viruses in the sample.

Virome● Whole genome must be done to identify the

viruses in the sample.

● They took human blood and extracted nucleic acid from it and did very high throughput sequencing (NGS).

● The sequencing gave a good idea about the present nucleic acid, and the figure here to the right represent the results from that sequencing.

Virome● 67.7% of the sequences in the blood are viral.● 9.5% of the sequences are bacteria.● Only 3.6 % of the sequences are for eukaryota

including human.● The way we identify the sequences is by

comparing it to a database.●

Virome

● This figure is more detailed study of the human virome in every part of the body.

● There's a unique set of viruses that are listed here.

● DNA and RNA viruses at each of these locations.

● These viruses can be found in healthy humans.

● There is a huge virom in the human body and it is always changing.

Virome● What are we trying to understand now is, if the virom is beneficial or not, and

how can we manipulate it.

● We can get rid of bacteria by treatment with antimicrobials.

● We can't do this with viruses; we don't have that many antiviral that will simply wipe out your virome and then we can see what happens.

MNV reverses intestinal abnormalities in GF mice

An enteric virus can replace the beneficial function of commensal bacteria

Nature. 2014 Dec 4;516(7529):94-8. doi: 10.1038/nature13960. Epub 2014 Nov 19.

Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease.

● It was mentioned earlier that we have viral genetic sequence as part of the human DNA.

3.2 billion bases

The human genome

● 3.2 billion bases and it is divided up into the different parts that is shown in the pie chart.

● Protein coding genes are 1.5% of the DNA. (the minority of the DNA actually encodes proteins)

● The rest of the genome is all sort of stuff, we are just in the beginning to understand, like introns, heterochromatin, duplicated sequences, interspersed elements like lines and signs.

● 8.3% LTR retrotransposons, many of these are retroviral DNAs; a virus called retroviruses that is an RNA virus that inverts its genome into DNA and then integrates it into the infected cell.

The human genome● Many animals on earth have experienced retroviral infection.● Those DNAs integrated into chromosomes of the animals, are passed on to

their children and so forth.● Most of these sequences don't make infectious viruses.● But turns out that many of the proteins have been exapted.● Exapted protein means you take a virus protein and use it to your own

purposes.● We have exapted a number of retroviruses genes for our own use over the

years.

Why not?● Most viruses pass through us, we ingest many non-animal viruses regularly

with food.- Metagenomic analysis in human feces reveal that most viral sequences are similar to plant viruses.- 91% of the obtained sequences are for plant viruses.

● We have an amazing immune system.

Our immune system

● The figure on the right diagram the work of the immune system.

● The immune system takes care of any viral infection.

Eclipse: viruses parts are builtBurst: Viruses are assembled